Association of the genetic variants of APOA5 and PRKCH with hypertension in community-dwelling Japanese individuals

Abstract

Hypertension is a complex multifactorial disorder that is thought to result from the interaction between genetic background and environmental factors. Although various loci and genes have been implicated in the predisposition to hypertension by genetic linkage analyses and candidate gene association studies, the genes that confer susceptibility to this condition remain to be identified definitively. We have now examined the relation of five candidate gene polymorphisms to blood pressure (BP) and the prevalence of hypertension in an 8-year population-based longitudinal cohort study. The 2267 subjects (1128 women, 1139 men) were aged 40-79 years and were randomly recruited to a population-based prospective cohort study of aging and age-related diseases in Japan. BP was measured after subjects had rested in a sitting position for at least 15 min. Genotypes for the -765G↷C polymorphism of PTGS2 and the 67G↷A (Ala23Thr) polymorphism of CCL11 were determined using a fluorescence-based allele-specific DNA primer assay system, and those of the 1444T↷C (3'-UTR) polymorphism of CRP, the -1131T↷C polymorphism of APOA5 and the 1425G↷A (Val374Ile) polymorphism of PRKCH using melting curve analysis. Longitudinal analysis of the relation between systolic or diastolic BP and the five polymorphisms with a mixed-effect model revealed that the polymorphism of CRP was significantly related to systolic BP in all subjects, that of APOA5 to systolic BP in men, and that of PRKCH to diastolic BP in women. Longitudinal analysis of the relation between the prevalence of hypertension and the five polymorphisms with a generalized estimating equation revealed that the CRP, APOA5 and CCL11 polymorphisms were significantly related to the prevalence of hypertension in men, the PTGS2 polymorphism to its prevalence in all subjects, and the PRKCH polymorphism to its prevalence in all subjects and in women. The APOA5 and PRKCH polymorphisms were thus associated with both BP and the prevalence of hypertension in men and women, respectively. These results suggest that the APOA5 and PRKCH polymorphisms are determinants of BP and the development of hypertension in Japanese men and women, respectively.